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Biomedical subjects

K Tada

Publications and source records attributed to K Tada.

At least 73 records · Page 4Linked to original sources
PubMed1999

Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation.

TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-kappaB and c-Jun NH(2)-terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-beta receptor. To investigate the functional role of TRAF5 in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-kappaB or c-Jun NH(2)-terminal kinase/stress-activated protein kinase by tumor necrosis factor, CD27, and CD40 was not abrogated in traf5(-/-) mice. However, traf5(-/-) B cells showed defects in proliferation and up-regulation of various surface molecules, including CD23, CD54, CD80, CD86, and Fas in response to CD40 stimulation. Moreover, in vitro Ig production of traf5(-/-) B cells stimulated with anti-CD40 plus IL-4 was reduced substantially. CD27-mediated costimulatory signal also was impaired in traf5(-/-) T cells. Collectively, these results demonstrate that TRAF5 is involved in CD40- and CD27-mediated signaling.

Animals↗
PubMed1999

Selective expression of a novel surface molecule by human Th2 cells in vivo.

The search for reliable marker molecules discriminating between human Th1 and Th2 cells identified a gene encoding a novel member of the G protein-coupled leukocyte chemoattractant receptor family, which is selectively expressed in Th2 but not Th1 lineage cells, thereby named CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells). Studies with anti-CRTH2 mAbs demonstrated that CRTH2 was expressed in a small population (0.4-6.5%) of CD4+ T cells in fresh PBMCs of healthy adults, but no remarkable expression was seen in B cells and NK cells. In some cases, CD8+ T cells ( approximately 3.5%) expressed CRTH2. Phenotypes of CD4+ T cells expressing CRTH2 were CD45RA-, CD45RO+, and CD25+, similar to those of Ag-activated effector/memory T cells. Freshly isolated CRTH2+ CD4+ T cells produced Th2- but little or no Th1-type cytokines upon stimulation with PMA and ionomycin. In addition, an allergen-induced proliferative response in fresh PBMCs was significantly and selectively reduced by subtracting CRTH2+ cells. Together, these results indicate that CRTH2 is selectively expressed in vivo in an activated state of Th2 cells including allergen-responsive Th2 cells, suggesting its pivotal roles in ongoing Th2-type immune reactions.

Adult↗
PubMed1999

Prenatal diagnosis of non-ketotic hyperglycinaemia: enzymatic diagnosis in 28 families and DNA diagnosis detecting prevalent Finnish and Israeli-Arab mutations.

Prenatal diagnosis for non-ketotic hyperglycinaemia (NKH) was performed by enzymatic analysis of chorionic villus samples in 28 families and by DNA analysis in two families. In 26 families, enzymatic analysis of the glycine cleavage multi-enzyme system (GCS) yielded an unambiguous diagnosis; inconclusive results in two families were due to borderline GCS activity. We analysed a second chorionic sample in these two families. In one case, GCS activity was normal in the second specimen, and the baby did not have NKH. In the other case, we again found extremely low GCS activity in the second specimen, but a healthy baby was born. The cause of this false-positive result is unknown. Molecular analysis of NKH has identified two prevalent mutations to date; the S564I mutation in a gene encoding the P-protein, a component of the GCS, in a Finnish population, and the H42R mutation in a gene encoding the T-protein in the Israeli-Arab population. These prevalent mutations allow us to obtain unambiguous prenatal diagnoses in both Finnish and Israeli-Arab families. GCS activity in samples from a Finnish family demonstrated a good agreement with DNA analysis, but the fetus of the Israeli-Arab family had an upper limit activity of the affected range, suggesting an advantages for DNA analysis.

Amino Acid Oxidoreductases↗
PubMed1999

Laparoscopic resection of large leiomyomas of the gastric fundus.

Two patients with a large leiomyoma arising from the gastric fundus underwent laparoscopic resection. In case 1, the tumor was located in the anterior wall of the gastric fundus. To prevent stenosis and preserve the volume of the residual stomach, intragastric resection was adopted. The tumor was markedly and resected with laparosonic coagulating shears with a 1-cm safety margin. In case 2, a large tumor was detected in the duodenal bulb. Serious hemorrhage mandated emergency resection. The tumor originated from the posterior wall of the fundus. Attempts at reduction with the forceps failed. Reduction by digital manipulation via laparoscopic port sites was successful. An endostapler was used to resect the tumor and close the anterior wall. Both patients recovered uneventfully.

Aged↗
PubMed1999

Limonoids from fruit of Melia toosendan and their cytotoxic activity.

Two new limonoids, toosendanal and 12-O-methylvolkensin, were isolated from the fruits of Melia toosendan Sieb. et Zucc. along with three known limonoids, meliatoxin B1, trichillin H, and toosendanin. The structures of the new limonoids were established by spectroscopic methods, with toosendanal having C-1/C-29 and C-19/C-29 acetal bridges. Both meliatoxin B1 and toosendanin exhibit cytotoxic activity against KB cells.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Parvovirus B19 infection induces apoptosis of erythroid cells in vitro and in vivo.

OBJECTIVE: intrauterine parvovirus B19 infection is related to non-immune hydrops fetalis, the pathogenesis of which is based on the strict tropism of B19 for erythroid precursor cells and the massive destruction of the infected erythroid cells, although the mechanism of beta19-induced cytotoxicity has not been studied in detail. The purpose of this study is to provide empirical evidence that beta19 induces apoptosis of erythroid cells both in vitro and ill vivo. METHODS: we analysed culture cells infected in vitro by B19 and tissues of nine cases of hydrops fetalis caused by B19 intrauterine infection by histological and biological methods. RESULTS: cells infected iil vitro by B19 showed nuclear changes characteristic of apoptosis by light microscopic examination and DNA extracted from the infected cells was fragmented. Electron microscopic examination showed the nuclei of infected cells contained crescent-shaped clumps of heterochromatin with increased density and double staining with anti-B1 9 antibody and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) confirmed apoptosis of individual cells. Tissues of cases of hydrops fetalis caused by B19 contained erythroid cells with nuclear inclusions and characteristic nuclear changes of apoptosis by light microscopy. The double-staining confirmed apoptosis of erythroid cells in the tissues. Immunohistochemical analysis with antibodies against cellular factors involved in apoptosis showed that caspase3, p53 and p21 were positive in infected cells.

Apoptosis↗
PubMed1999

Pilot study of screening for Wilson disease using dried blood spots obtained from children seen at outpatient clinics.

Wilson disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. In this paper, we describe the results of a pilot study of screening for WD using ceruloplasmin determinations in dried blood samples. Specimens were collected from children aged 1 to 6 years who were seen at local paediatric outpatient clinics in the Miyagi Prefecture. We measured ceruloplasmin (CP) concentrations in 2789 children using an enzyme-linked immunosorbent assay. The mean value was 12.4 +/- 3.95 mg/dl blood. Among these children, we identified two (case 1, male, 2 years old; case 2, female, 3 years old) with markedly reduced CP concentrations. Apart from low serum copper concentrations, their biochemical findings were almost normal, as were growth and development. To confirm the diagnosis, we analysed the WD gene and detected A803T/2871delC mutations in case 1 and R778L/G1035V mutations in case 2. We conclude that these children were presymptomatic WD patients. The CP level in dried blood samples from children aged 1 to 6 years appears to be a reliable marker for early detection of WD.

Ceruloplasmin↗
PubMed1999

Region between alpha-helices 3 and 4 of the mad homology 2 domain of Smad4: functional roles in oligomer formation and transcriptional activation.

BACKGROUND: Smad4 has a unique region of 35 amino acids between alpha-helices 3 and 4 (termed H3/4 loop) of the Mad homology (MH) 2 domain. In order to elucidate the functional importance of the H3/4 loop, we prepared chimeric constructs of Smad4 containing the region corresponding to the alpha-helix 3, H3/4 loop and alpha-helix 4 of different Smads, including a chimera containing that of Smad2 (Smad4-HL2). RESULTS: Smad4-HL2 constitutively induced the transcriptional activation of p3TP-Lux, a TGF-beta-responsive reporter construct. However, co-transfection of Smad2 with Smad4-HL2 did not induce a further increase in the activation of p3TP-Lux. Smad4-HL2 did not induce the activation of pAR3-Lux, which contains FAST1-binding sites and is activated by a complex composed of FAST1, Smad2 and Smad4. Smad4-HL2 formed a homo-oligomer more efficiently than wild-type Smad4 in mammalian cells. Moreover, Smad4-HL2 bound to DNA containing the Smad-binding sites with a gretaer affinity than the wild-type Smad4. CONCLUSION: Smad4-HL2 spontaneously forms a homo-oligomer, which may bind to DNA with relatively high affinity and induce transcriptional activation of p3TP-Lux. The H3/4 loop of Smad4 may thus play a role in precluding the spontaneous oligomer formation of Smad4.

Animals↗
PubMed1999

Generation of peroxynitrite and apoptosis in placenta of patients with chorioamnionitis: possible implications in placental abruption.

The reaction of nitric oxide (NO) and superoxide results in the formation of peroxynitrite, a potent and relatively long-lived oxidant. In infectious diseases, these molecules are not only bactericidal but also toxic to host cells. Chorioamnionitis is often complicated by premature rupture of membranes and can be associated with placental abruption. These diseases are significant causes of premature low-birth-weight deliveries and consequently the morbidity and mortality of neonates. Lipopolysaccharide, bacterial endotoxin, is known to be elevated in the amniotic fluid of patients with chorioamnionitis. Lipopolysaccharide is known to induce the formation of NO and superoxide. We report here that nitrite/nitrate, stable metabolites of NO, were increased in serum from patients with chorioamnionitis. Immunohistochemical studies demonstrated enhanced expression of inducible NO synthase and formation of nitrotyrosine, a footprint of peroxynitrite, in the placentae from patients with chorioamnionitis and also in patients with placental abruption. Furthermore, apoptotic cell death was also increased in the placentae from patients with both diseases. These results suggest that chorioamnionitis and a portion of placental abruption may share a common cascade of placental injury. Nitric oxide and its metabolities may play an important role in this cascade.

Adult↗
PubMed1999

Clinical experience of long-term transdermal treatment with nitric oxide donor for women with preeclampsia.

Isosorbide dinitrate (ISDN), a nitric oxide donor, was applied transdermally for 4-16 days to 4 preeclamptic women with oligohydramnios, intrauterine fetal growth retardation (IUGR), and elevated resistance of blood flow in the uterine arteries. Pulsed Doppler ultrasonography revealed immediate and drastic improvement of pulsatility index (PI) of uterine arteries following treatment with ISDN. The average PI in uterine arteries of the 4 patients was reduced to approximately 67% of that of the untreated state. In 2 patients the amniotic fluid gradually increased over a few days which suggested improvement of fetoplacental circulation during administration of ISDN. This study suggests that long-term transdermal ISDN is an effective therapy, at least in a portion of preeclamptic women, to avoid maternal hypertension, fetal distress, oligohydramnios, and IUGR, and consequentially to prolong the gestational period.

Administration, Cutaneous↗
PubMed1999

Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation.

Bone morphogenetic protein (BMP)-6 is a member of the transforming growth factor (TGF)-(&bgr;) superfamily, and is most similar to BMP-5, osteogenic protein (OP)-1/BMP-7, and OP-2/BMP-8. In the present study, we characterized the endogenous BMP-6 signaling pathway during osteoblast differentiation. BMP-6 strongly induced alkaline phosphatase (ALP) activity in cells of osteoblast lineage, including C2C12 cells, MC3T3-E1 cells, and ROB-C26 cells. The profile of binding of BMP-6 to type I and type II receptors was similar to that of OP-1/BMP-7 in C2C12 cells and MC3T3-E1 cells; BMP-6 strongly bound to activin receptor-like kinase (ALK)-2 (also termed ActR-I), together with type II receptors, i.e. BMP type II receptor (BMPR-II) and activin type II receptor (ActR-II). In addition, BMP-6 weakly bound to BMPR-IA (ALK-3), to which BMP-2 also bound. In contrast, binding of BMP-6 to BMPR-IB (ALK-6), and less efficiently to ALK-2 and BMPR-IA, together with BMPR-II was detected in ROB-C26 cells. Intracellular signalling was further studied using C2C12 and MC3T3-E1 cells. Among the receptor-regulated Smads activated by BMP receptors, BMP-6 strongly induced phosphorylation and nuclear accumulation of Smad5, and less efficiently those of Smad1. However, Smad8 was constitutively phosphorylated, and no further phosphorylation or nuclear accumulation of Smad8 by BMP-6 was observed. These findings indicate that in the process of differentiation to osteoblasts, BMP-6 binds to ALK-2 as well as other type I receptors, and transduces signals mainly through Smad5 and possibly through Smad1.

3T3 Cells↗
PubMed1999

The relationship between the site of nonunion of the scaphoid and scaphoid nonunion advanced collapse (SNAC).

We studied retrospectively the radiographs of 33 patients with late symptoms after scaphoid nonunion in an attempt to relate the incidence of scaphoid nonunion advanced collapse (SNAC) to the level of the original fracture. We found differing patterns for nonunion at the proximal, middle and distal thirds. The mean intervals between fracture and complaint were 20.9, 6.7 and 12.6 years and obvious degenerative changes occurred in 85.7%, 40.0% and 33.3%, for the six proximal-, eight middle- and two distal-third nonunions, respectively. Nonunion at the proximal and middle thirds showed the first degenerative changes at the radioscaphoid joint, and this was followed by narrowing of the scaphocapitate and then the lunocapitate joints. In our two nonunions of the distal third degenerative changes were seen only at the lunocapitate joint. Most patients with SNAC and nonunion of the middle or distal third showed dorsal intercalated instability; few patients with nonunion of the proximal third developed this deformity. We discuss the initial management of nonunion of the scaphoid at different levels in the light of our findings, and make recommendations.

Adolescent↗
PubMed1999

[Effects of aging and hyperlipidemia on plasma osteopontin level].

In order to elucidate a possible mechanism for accelerated atherogenesis as well as enhanced vascular calcification observed during the normal aging process, we measured plasma osteopontin (OPN) levels and examined their relation to aging and certain disease parameters. In all cases examined, no significant relation was found between the plasma OPN level and age, body mass index, blood pressure, plasma levels of glucose and insulin, serum levels of creatinine, triglyceride, and high density lipoprotein cholesterol. On the other hand, a significant negative correlation was found between the plasma OPN level and serum total cholesterol concentration (n = 78, r = -0.355, p = 0.0014). The serum level of low density lipoprotein (LDL) cholesterol, calculated by the formula of Friedewald, also showed a significant negative correlation to the plasma OPN level (n = 78, r = -0.301, p = 0.0075). In cases without diabetes mellitus and hypertension, a significant positive correlation was found between the plasma OPN level and age (n = 22, r = 0.445, p = 0.0378). It is postulated that OPN plays a negative regulatory role in the development of vascular calcification. Therefore, the observed negative relationship between the plasma OPN level and the serum levels of total cholesterol and LDL cholesterol, suggests a possibility that hypercholesterolemia facilitates vascular calcification by suppressing OPN synthesis. On the other hand, in non-diabetic and normotensive cases, the positive relationship between the plasma OPN level and age may reflect a defense mechanism against age-related increase of vascular calcification.

Aging↗
PubMed1999

Peripheral nerve palsies in victims of the Hanshin-Awaji earthquake.

On January 17, 1995, the Hanshin-Awaji earthquake directly hit a metropolis and destroyed approximately 120,000 houses. Many people were buried under the debris of the Japanese style wooden houses or were injured by falling furniture. Twenty-five patients (35 extremities) with earthquake associated peripheral nerve palsy were studied and followed up for 2 years. The characteristic feature of earthquake associated palsies was combined nerve palsy induced by prolonged compression. There were 11 extremities with brachial plexus palsy; two extremities with combined radial, median, and ulnar nerve palsy; two extremities with combined median and ulnar nerve palsy; two extremities with radial nerve palsy; two extremities with ulnar nerve palsy; 10 extremities with combined femoral and sciatic nerve palsy; one extremity with combined tibial and peroneal nerve palsy; and five extremities with compartment syndrome of the leg. Many peripheral nerve palsies were induced by nerve ischemia. Most patients had good spontaneous recovery. The prognosis of these palsies generally was good.

Adolescent↗
PubMed1999

Association between drinking-related antisocial behavior and a polymorphism in the serotonin transporter gene in a Japanese population.

BACKGROUND: Involvement of the serotoninergic system (S/S) in alcoholism has been suggested in both mice and humans. Previous studies have suggested the S/S genotype of the serotonin transporter gene promoter polymorphism to be associated with severe alcohol dependence marked by severe withdrawal symptoms. It has also been associated with alcoholics who exhibit a dissocial personality disorder. METHODS: We examined the polymorphism in 166 Japanese alcoholics who experienced withdrawal seizure or delirium and 290 Japanese controls. RESULTS: The S/S genotype was not increased in the patients. Exploratory analyses showed significantly less frequent S allele and S/S genotype frequencies in the alcoholics with a history of drinking-related arrests than in the controls (p = 0.009 and p = 0.03, respectively), perhaps reflecting previously reported harm avoidance personality traits associated with S/S. Alcoholics with the L allele had a significantly earlier onset of alcohol dependence than those with the S/S genotype (p = 0.01). CONCLUSIONS: The present study failed to provide supportive evidence for an association of the S/S genotype with severe alcoholism marked by physical withdrawal symptoms or with antisocial behaviors among the Japanese. Although our data support involvement of the central serotoninergic system in some types of alcoholism, the potential association findings of this study emerged as only exploratory and, therefore, should be understood as tentative until replicated in other studies.

Adult↗
PubMed1999

[Pancreatic pleural effusion accompanied by bronchopleural fistula].

In recent years, chronic massive pleural effusions have been increasingly recognized as a serious complication of pancreatitis. We describe the third reported case of a pancreatic pleural effusion accompanied by bronchopleural fistula. A 49-year-old man suffering from chronic alcohol-related pancreatitis was admitted to our hospital complaining of cough and shortness of breath. A chest x-ray film disclosed a large right pleural effusion with an air-fluid level. Ultrasonography and computed tomography of the upper abdomen demonstrated a giant pancreatic pseudocyst in the pancreatic tail and a fistulous tract reaching into the posterior mediastinum via the esophageal hiatus. Thoracentesis revealed sterile hemorrhagic fluid with markedly elevated amylase activity of 20,955 IU/l (pancreatic isozyme, 100%) and no malignant cells. A diagnosis of pancreatic pleural effusion was made. The therapy for pancreatic internal fistula is somewhat controversial. We employed conservative therapy, including hyperalimentation and chest tube drainage that successfully decreased the pleural effusion and closed the fistulous tract. Nonetheless, we were still troubled by a continuous air-leak via the drainage tube. Pleurodesis confirmed the tentative diagnosis of bronchopleural fistula and successfully stopped the air-leak. No re-accumulation of pleural effusion has been seen for 2 years. We concluded that pancreatic enzyme-rich effusions, if long-standing, may be complicated by bronchopleural fistula, thus underscoring the need for urgent drainage and initially conservative management.

Bronchial Fistula↗